1. Field of the Invention
This invention relates to optical isomer separating agents using ovomucoid the molecular structure of which is partly modified.
2. Description of Related Arts
For chiral chemical substances containing asymmetric carbon atoms, the separation of their optical isomers is strongly desired, particularly, in the field of pharmaceuticals. Namely, it has been established as a general fact that one of a plurality of optical isomers constituting one racemic body shows particularly remarkable pharmaceutical utilities, for example, remarkable pharmacological effect and remarkable availability in vivo, or conversely, remarkable toxicity, and thus, as pharmaceuticals, administration in the form of a separated optical isomer is more rational than that in the form of a racemic body, resulting in an enhancement in remedial effect.
Various laboratory methods for separation of optical isomers have been reported so far, but those practicable in industrial scale are few, which has been considered to be an extremely difficult technical problem. However, in accordance with the progress of column chromatography, particularly, the separation of optical isomers by liquid chromatography comes to be known, as shown in following references (1)-(3).
(1) D. W. Armstrong et al., Journal of Chromatographic Science, Vol. 22 (1984), 411-415. PA0 (2) Jorgen Hermansson, Journal of Chromatography, 325 (1985), 379-384. PA0 (3) I. W. Wainer et al., Journal of Chromatography, 284 (1984), 117-124. PA0 (4) S. Allenmark et al., Journal of Chromatography, 264 (1983), 63-68. PA0 (5) S. Allenmark et al., Journal of Chromatography, 237 (1982), 473-477. PA0 (6) U. S. Pat. No. 4,539,399 PA0 (7) Japanese Patent Application OPI No. 60-41619 PA0 (8) T. Miwa et al., Chemical and Pharmaceutical Bulletin, Vol. 35 (1987), 682-686.
Among the references described above, (1) discloses the separation using cyclodextrin, and (6) discloses the separation using a stationary phase having cyclodextrin bonded to silica gel. (2) discloses a technique using 1-acidic glycoprotein, and (3) discloses a technique using (R)-N-(3,5-dinitrobenzoyl)phenylglycine. (4) and (5) disclose the separation using stationary phases having bovine serum albumin bonded to silica and agarose, respectively. (7) discloses the separation using orosomucoid and its functional analogs, and (8) discloses the separation using a stationary phase having ovomucoid bonded to a carrier.
However, the materials used in the techniques of (1)-(7) are generally expensive. Further, as these techniques mainly adopts liquid chromatographic separation requiring large quantities of organic solvents, the used materials must be stable to the deformation of the organic solvents. However, albumin and ovomucoid, for example, can not sufficiently satisfy this condition.
In the method of (8), a comparatively inexpensive material, ovomucoid, is used in the form of an optical isomer separating agent by bonding it to silica gel, cellulose, or synthetic polymers, but this method has a disadvantage in that much time is required for re-equilibration at the time of eluate exchange, and also,, optical resolution is often insufficient. For example, propranolol and alprenolol which are .beta.-blockers does not provide sufficient optical resolution.